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- Prazosin
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Dr. Ray Shahelien entry: 

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Prazosin is a centrally active antagonist of the α1-adrenoreceptor (α1-AR) in the noradrenergic system. This drug is used for a number of applications, not just hypertension.

http://www.drugs.com/mmx/prazosin-hydrochloride.html

http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/996308064?r=640303564#640303564

The noradrenergic system plays an important role in learning and memory. Moderate levels of norepinephrine released under control conditions strengthen prefrontal cortical functions via actions at post-synaptic α-2A adrenoceptors with high affinity for norepinephrine, while high levels of norepinephrine release during stress impair prefrontal cortex (PFC) cortical functions via α1 and possibly β1 receptors with lower affinity for norepinephrine. Thus, levels of norepinephrine determine whether prefrontal cortical or posterior cortical systems control behavior and thought. The successful use of atypical antipsychotics is thought to be related to their α1- and 5HT2A-blocking properties.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151919/

Aggressive behavior is associated with an increase in the number of α1-adrenoceptors in AD patients.
http://www.ncbi.nlm.nih.gov/pubmed/17463193

Two successful trials for treating AD agitation and aggression with Prazosin:

PRAZOSIN FOR THE TREATMENT OF BEHAVIORAL SYMPTOMS IN ALZHEIMER’S DISEASE PATIENTS WITH AGITATION AND AGGRESSION
Am J Geriatr Psychiatry. Author manuscript; available in PMC 2010 September 1.
Published in final edited form as:
Am J Geriatr Psychiatry. 2009 September; 17(9): 744–751.
doi: 10.1097/JGP.0b013e3181ab8c61.

This study provides preliminary support for the efficacy of the alpha-1 AR antagonist prazosin as a novel treatment for behavioral symptoms in AD patients with agitation and aggression.
PMCID: PMC2842091 NIHMSID: NIHMS181108
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842091
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842091/pdf/nihms181108.pdf

http://www.alzheimersanddementia.com/article/PIIS1552526008015136/fulltext

Two larger trials are now recruiting (as of October, 2010):
http://clinicaltrial.gov/ct2/show/NCT01126099
http://clinicaltrial.gov/ct2/show/NCT00161473

Changes in noradrenergic neurons appear to be similar in AD and Lewy body patients.
http://neuro.cjb.net/cgi/content/full/26/2/467

It is therefore conceivable that prazosin might help LBD patients who are sensitive to antipsychotics.


Long-lasting memories of aversive or stressful events have been associated with the noradrenergic system activation. Traumatic stressors are thought to lead to excessive norepinephrine release and α1-AR engagement. Animal research suggests that high levels of α1-AR stimulation should weaken PFC inhibitory functions and strengthen amygdala function, the profile observed in posttraumatic stress disorder (PTSD). The high CNS noradrenergic outflow in PTSD is thought to stimulate α1-adrenergic regulation of the prefrontal cerebral cortex, disrupting cognitive processing and increasing fear responses.

Trauma-related nightmares in PTSD rarely respond to pharmacologic treatment. However, low doses of prazosin have been found to substantially reduced nightmares and moderately or markedly reduced overall PTSD severity and function in previously treatment-resistant combat veterans. Given an hour before bedtime, low doses of prazosin reduce light sleep, normalize REM sleep, and increase total sleep time. An additional daytime dose was found to reduce residual daytime symptoms of civilian trauma victims.
http://www.ncbi.nlm.nih.gov/pubmed/10732660
http://ajp.psychiatryonline.org/cgi/content/full/160/2/371
http://www.ncbi.nlm.nih.gov/pubmed/16460691
http://www.ncbi.nlm.nih.gov/pubmed/11799347
http://www.ncbi.nlm.nih.gov/pubmed/12967060
http://www.theannals.com/cgi/content/full/41/6/1013?ijkey=d792a3ea4dc2c2257480eb0df62ba985fcd77d57

The drug is now commonly used for this application, and there are quite a few clinical trials ongoing, as well.

Some of our members are dealing with ADLOs who suffer from PTSD. And I've gotten the impression that the AD worsens the PTSD symptoms. So perhaps prazosin may offer them some relief, too.

Fatigue is the most common side effect.

Note that the levels of prazosin that are reported to be effective for treating PTSD are much lower than those that are used to treat hypertension.

For those who are interested, here is an overview of the way in which various drugs for treating insomnia, parasomnias, and circadian rhythm disorders are thought to work:
http://www.bap.org.uk/pdfs/BAP_Sleep_Guidelines.pdf

Prazosin helps in the memory of aged mice:

http://www.springerlink.com/content/lfab9e8cv19kblwt/fulltext.pdf

A slide show presentation of controlled outcome double-blind research looking at effects of risperidone, olanzapine, and prazosin on agitation and related behaviors in AD patients:
http://depts.washington.edu/adrcweb/RaskindPresentation061808.pdf

Apparently, all the current major prazosin research is coming out of Washington state via Dr. Raskind.
http://www.sciencedaily.com/releases/2007/11/071106174204.htm


http://ajp.psychiatryonline.org/cgi/reprint/154/1/25.pdf


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Updated: July 2, 2012
Inception: July 2, 2012